A nerve fiber is composed of an axon passing through the center of the fiber and a myelin sheath surrounding the outside thereof. A major component of the myelin sheath is a lipid, and it is involved in a mechanism of promoting the electrical conduction of the nerve. Demyelinating disease is one type of neurological disease, which is developed when the myelin sheath is destroyed (demyelination change). This disease is caused by a viral infection, poisoning by alcohol and the like, malnutrition, etc. However, some demyelinating diseases are developed by an unknown cause (idiopathic demyelination). It has been assumed that the demyelinating disease would be developed by immune abnormality such as allergy or autoimmunization. In the demyelinating disease, a variety of symptoms such as movement disorders and sensory disorders in eyes, face, mouth, tongue, throat, hands and feet, and rectum and/or bladder disorders, appear as complicated and entangled elements. The demyelinating disease includes a central demyelinating disease and a peripheral demyelinating disease. Examples of the central demyelinating disease include multiple sclerosis (neuromyelitis optica (Devic syndrome) and concentric sclerosis (Balo's disease)), acute disseminated encephalomyelitis, inflammatory diffuse sclerosis (Schilder's disease), sub-acute sclerosis panencephalitis, progressive multifocal leukoencephalopathy, cerebral hypoxia, central pontine myelinolysis, vitamin B12 deficiency, and Binswanger's disease. Examples of the peripheral demyelinating disease include Guillain-Barre syndrome and chronic inflammatory demyelinating polyneuropathy.
On the other hand, in 1992, from haploid myxamoebae of Physarum polycephalum, a lipid-soluble substance, which is capable of suppressing the activity of DNA polymerase α that is a DNA polymerase enzyme for eukaryotic cells and suppressing proliferation of cultured animal cells, has been discovered and has been then isolated and purified (Murakami-Murofushi, K., et al., J. Biol. Chem. 267, 21512-21517 (1992)). This substance has been found to be a substance in which hexadecanoic acid containing cyclopropane binds to the sn-1 position of the glycerol backbone and phosphoric acid binds to each of the sn-2 and sn-3 positions via a cyclic ester bond. Since this substance is an LPA-like substance derived from Physarum, it has been named as “PHYLPA,” PHYLPA has a characteristic fatty acid chain in the sn-1 position. Thus, a derivative in which the characteristic fatty acid chain was replaced with a general fatty acid chain, was chemically synthesized, and the activity thereof was then examined. As a result, it was demonstrated that the derivative suppresses cell proliferation, and thus, it was revealed that the proliferation-suppressing action of PHYLPA is caused by the cyclic phosphate groups in the sn-2 and sn-3 positions. At present, LPA analogs having such cyclic phosphate groups are collectively referred to as a “cyclic phosphatidic acid (cPA).”

With regard to the cyclic phosphatidic acids and their derivatives, there have been several reports regarding an action as a neurotrophic factor and application thereof to neurodegenerative diseases (Patent Literatures 1 and 2), suppression of the proliferation, invasion and/or metastasis of cancer cells (Patent Literature 3), analgesic action (Patent Literature 4), and application to atopic dermatitis (Patent Literature 5). However, there have been no findings regarding the influence of the cyclic phosphatidic acid and their derivatives on demyelination of nerve axons.